This project is involved in the detailed, longitudinal evaluation and treatment of patients with acute and chronic psychiatric illness, including depression, mania, schizoaffective illness, and drug-induced psychoses. The major research strategies include: precise longitudinal behavioral and biological measurements in the context of double-blind clinical trials of both routine and new, specific pharmacological agents. Neurotransmitter amines, metabolites, enzymes, electrolytes, cyclic nucleotides, polypeptide and related biological regulatory compounds are measured in body fluids of patients on and off medications and in different phases of illness and recovery. Neuroendocrine, motor activity, sleep, and averaged evoked responses are also monitored as well as specific measures of mood, cognition, abstraction, and verbal learning. An active animal and primate laboratory is maintained for the development of new techniques, including behavioral-biological studies not feasible in man, and studying animal "models" of psychosis, such as chronic cocaine-induced behavioral changes in the monkey and electrical kindling. An active interplay of psychological and biological perspectives thus occurs in seeking and developing new theories, research, and treatment approaches for a range of psychotic illnesses in man.